title: Rosiglitazone does not improve vascular function in subjects with chronic kidney disease.
abstract: BACKGROUND
  Thiazolidinediones such as rosiglitazone (RSG) are insulin-sensitizing agents, which may improve inflammation and vascular function, and thus potentially lower cardiovascular risk in patients with chronic kidney disease (CKD). However, there is growing concern about the adverse cardiovascular effects of RSG in diabetic patients without CKD, and the data in patients with CKD remain conflicting. This study examines the effect of RSG on vascular function in patients with CKD.
  
  
  METHODS
  A randomized, double-blind placebo-controlled study comparing RSG 4 mg daily (n = 35) with placebo (n = 35) for 8 weeks was performed in CKD subjects. Primary outcome measures were flow-mediated dilatation (FMD), systemic arterial compliance (SAC) and augmentation index (AIx). Secondary outcomes included glyceryl trinitrate-mediated dilatation (GTN-MD), pulse-wave velocity (PWV), lipids, blood pressure, homoeostasis model assessment (HOMA), adiponectin, high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity interleukin 6 (hs-IL-6) and in vivo marker of endothelial function [von Willebrand Factor (vWF)].
  
  
  RESULTS
  RSG lowered HOMA score [RSG geometric mean 1.7 (95% confidence interval 1.3-2.3); placebo 1.9 (1.4-2.5), P = 0.04], hs-CRP [RSG 1.2 (0.9-1.7) mg/L; placebo 1.6 (1.2-2.3), P = 0.04] and vWF [RSG mean 126.1 ± SD 45.7%; placebo 132.7 ± 41.7, P = 0.01] but not hs-IL-6. RSG did not significantly change arterial function (FMD, GTN-MD, SAC), arterial stiffness (AIx, PWV) or blood pressure. RSG increased triglyceride concentration [RSG 1.8 (1.3-1.9) mmol/L; placebo 1.5 (1.3-1.9), P = 0.01] without affecting other lipid and lipoprotein concentrations.
  
  
  CONCLUSIONS
  Short-term RSG therapy reduced insulin resistance, in vivo markers of inflammation and abnormal endothelial function but had no effect on arterial function and stiffness in patients with CKD.
authors.affiliation: School of Medicine and Pharmacology, Royal Perth Hospital Unit, University of Western Australia, Perth, Australia. doris.chan@health.wa.gov.au
authors.forename: Doris T
authors.initials: DT
authors.lastname: Chan
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Irish
authors.forename: Gursharan K
authors.initials: GK
authors.lastname: Dogra
mesh_terms: D054392:Adipokines / Q000097:blood; D000293:Adolescent; D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000150:complications*; D008055:Lipids / Q000032:analysis; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects*; D059289:Vascular Stiffness / Q000187:drug effects*; D055815:Young Adult
chemical_list: D054392:Adipokines; D007004:Hypoglycemic Agents; D007328:Insulin; D015850:Interleukin-6; D008055:Lipids; D008074:Lipoproteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002097:C-Reactive Protein